This is a descriptive cross-sectional study that aims to determine the distribution of the CFTR causing variant in a group of patients at a cystic fibrosis (CF) center in southern Brazil, as well as to describe causing variants that are treatable with mutation-specific drugs. Ninety-two patients from a CF reference center were assessed in this research, all of them with a clinical diagnosis of CF and both alleles identified with pathogenic variants. The most prevalent causing variants were F508del, R1162X, G542X, and N1303K. As for patients with a mutation-specific drug indication, 69.6 % were candidates for the use of Elexacaftor/Tezacaftor/Ivacaftor (Trikafta ® ), 44.6 % for the use of Tezacaftor/Ivacaftor ( Symdeko ® ), and 35.9 % for the use of Lumacaftor/Ivacaftor (Orkambi ® ). For the use of Ivacaftor (Kalydeco ® ), only two patients (2.2 %) were candidates following the Brazilian agency approval. According to the FDA, 10 patients would be candidates for Ivacaftor (10.9 %). Causing variants of classes I and II, which are related to a major severity of the illness, were identified in 135 of 184 alleles (73.3 %). In this study, more than 2/3 of the patients were candidates for the use of CFTR modulators therapy.

A 17-year-old male was admitted to hospital for fever, right periorbital edema, purulent rhinorrhea, and nasal obstruction for 3 days ( Figure 1A). He had been under treatment with antibiotic and corticoid for rhinosinusitis, with no improvement. Previous surgery was performed 6 months before for ''nasal polyposis.'' The anatomopathological (AP) highlighted polypoid inflammatory mucosa.Upon examination, he presented with peripalpebral edema on the right, conjunctival hyperemia with preserved ocular mobility and visual acuity and painless subcutaneous nodules on the right hemiface. Nasoendoscopy showed no changes in the left or nasopharynx; in the right, edema and mucosa hyperemia obstructing the upper airway and purulent rhinorrhea.Contrast computerized tomography (CT) of sinuses and orbit revealed extraconal infiltrating and expanding injury compromising orbit and right periorbit, with eyeball proptosis; maxillary, sphenoid sinus, ethmoidal cells, frontal sinus, and nasolacrimal duct were obliterated; and infiltration of the skin and subcutaneous on the right was identified ( Figure 1B and C).Abdomen CT revealed splenomegaly (15.5 cm). Pelvis and chest CT were normal. Serologies, rheumatic tests, hemoculture, uroculture, and Mantoux were negative. During admission, cefepime was commenced for febrile neutropenia. Biopsy of the lesion via nasal endoscopy in the right nasal cavity was performed with Epstein-Barr virus (EBV) checking positive. There was not enough material for diagnosis through immunohistochemistry due to the large amount of necrotic material.There was a gradual worsening of pancytopenia, increase in lactate dehydronagenase (LDH), and episode of right severe epistaxis, which was controlled with nasal packing. Bone marrow biopsy was carried out due to the suspicion of lymphoma, with negative result. Prednisone was initiated in lower doses, and new biopsy of the lesion in the right nasal cavity was performed through lateral rhinotomy, anatomopathology examination identified lymphoma. Extranodal natural killer /T-cell lymphoma, nasal type (ENKL) was confirmed by immunohistochemistry. Treatment with radiotherapy and outpatient chemotherapy was commenced.After 2 months, the patient was admitted to hospital with fever and pancytopenia. A treatment with piperacillin and tazobactam was commenced. As no response was observed, antibiotic treatment was changed to cefepime. Fever persisted, general condition worsening progressed, liver and renal failure occurred. Nephrotoxic and hepatotoxic drugs were suspended, with no improvement in the condition. A new abdominal CT was requested for investigation of the clinical worsening, which suggested lymphoma progression with renal and hepatic infiltration. There was no response to new pushes of corticosteroid therapy. Patient died on the 17th day of admission. Case 2An 86-year-old female, healthy, was referred to otorhinolaryngologist after 3 months of admission at another hospital due to acute rhinosinusitis with no response to clinical treatment. She reported nasal o...

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